Cancer research may identify altered genes that are causally implicated in oncogenesis. Several types of somatic mutations that result in altered activity of an oncogene or tumor suppressor gene have been identified, including base substitutions, insertions, deletions, translocations, and chromosomal gains and losses. Compelling evidence exists for a causal role for some chromosomal rearrangements in cancer (Rowley, Nat Rev Cancer 1: 245 (2001)). Recurrent chromosomal aberrations have been primarily characteristic of leukemias, lymphomas, and sarcomas. Less than 1% of the known, disease-specific chromosomal rearrangements are associated with epithelial tumors (carcinomas), although those cancers are much more common and contribute to a relatively large fraction of the morbidity and mortality associated with human cancer (Mitelman, Mutat Res 462: 247 (2000)). While hematological malignancies are often characterized by disease-specific chromosomal rearrangements, most solid tumors have a plethora of non-specific chromosomal aberrations. Karyotypic complexity of solid tumors is thought to result from secondary alterations acquired through cancer evolution or progression.
Cancer-related chromosomal rearrangements may result from two primary mechanisms. In one, promoter/enhancer elements of one gene are rearranged adjacent to a proto-oncogene, thus causing altered expression of an oncogenic protein. This type of translocation is exemplified by the apposition of immunoglobulin (IG) and T-cell receptor (TCR) genes to the MYC oncogene, leading to oncogene activation in B- and T-cell malignancies, respectively (Rabbitts, Nature 372: 143 (1994)). In the other mechanism, rearrangement results in the fusion of two genes, which produces a fusion protein that may have a new function or altered activity. This type of translocation is exemplified by the BCR-ABL gene fusion in chronic myelogenous leukemia (CML) (Rowley, Nature 243: 290 (1973); de Klein et al., Nature 300: 765 (1982)), which led to the rational development of imatinib mesylate that successfully targets the BCR-ABL kinase (Deininger et al., Blood 105: 2640 (2005)).
Recurrent MIPOL1-ETV1 genetic rearrangements are described herein, which are useful for diagnosis and therapeutic applications related to human epithelial tumors.